The first examples of nonenzymatic N-oxidation of heteroarenes in the presence of amines are reported. Pyridine, quinoline, and isoquinoline N-oxides are selectively formed in the presence of more reactive aliphatic and alicyclic amines by use of an in situ protonation strategy and an iminium salt organocatalyst. Application to late-stage functionalization that mimics phase 1 metabolism of small-molecule drugs is also demonstrated.

University of Virginia, like many other universities, has developed a chemistry outreach program (called Chemistry Learning through Experimentation, Awareness, and Demonstration; i.e., Chemistry LEAD) that visits K–5 schools and teaches inquiry-based chemistry lessons in order to engage local students with science. Chemistry LEAD is graduate student organized and led. The number of classrooms the group can visit in any year is limited; consequently, to extend their impact, the group decided to organize a summer, 1 day professional workshop for teachers. The goal was to give teachers the knowledge, confidence, and materials necessary to implement inquiry-based chemistry lessons. The graduate students worked as a team, with different students leading different activities, to decrease the burden of workshop planning and implementation. The workshop was repeated for two summers; a total of 52 teachers from six school districts participated. The teachers enjoyed learning from the graduate students, and follow-up surveys revealed they improved their understanding of inquiry and had more confidence in implementing inquiry-based chemistry lessons. Indeed, most teachers implemented at least one of the investigations they learned during the workshop and indicated their students were highly engaged during the activities. Graduate students’ reflections indicated that they gained skills in communication, planning, and delegation that will be useful to them in a variety of career paths. These workshops were a manageable way for the graduate student outreach group to increase their impact and improve chemistry education in local K–5 classrooms.

Carbon–nitrogen bonds are extremely prevalent in pharmaceuticals, natural products, and other biologically relevant molecules such as nucleic acids and proteins. Intermolecular amination of C­(sp3)–H bonds by catalytic nitrene transfer is a promising method for forging C–N bonds. An organocatalytic approach to nitrene transfer by way of an iminium salt offers a site-selective method for C­(sp3)–H amination. Understanding of this amination mechanism including the nature of the relevant intermediates and the factors controlling the mechanism of the N–H bond formation step would aid in the design of catalysts and C­(sp3)–H amination methods. In this work, the mechanism of the iminium salt-catalyzed C­(sp3)–H amination via nitrene transfer was elucidated computationally using quantum mechanical methods and molecular dynamics simulations. Dispersion-corrected density functional theory calculations provide support for an open singlet biradical species in equilibrium with the lower energy triplet species. Calculations further reveal that, while the singlet biradical species undergoes N–H bond formation by a hydride transfer process, the triplet species forms the N–H bond by H-atom abstraction. Molecular dynamics simulations rule out the possibility of a fast rebound of the carbon substrate following N–H bond formation. A predictive model for mode of activation and site selectivity that is consistent with experimental observations is presented.

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